1995 Fiscal Year Final Research Report Summary
Role of Ras and Ras-relatd protein for carcinogenesis of endometrial
Project/Area Number |
05671379
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
Obstetrics and gynecology
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Research Institution | Kyshu University |
Principal Investigator |
KATO Kiyoko Medical Institute of Bioregulation Kyushu Univ. Lecturer, 生体防御医学研究所, 助手 (10253527)
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Co-Investigator(Kenkyū-buntansha) |
WAKE Norio Medical Institute of Bioregulation Kyushu Univ. Professor, 生体防御医学研究所, 教授 (50158606)
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Project Period (FY) |
1993 – 1995
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Keywords | Ras / Singnal transduction / EGF recepter / Endmetrial carcinoma |
Research Abstract |
Since the majority of endometrial carcinomas do not contain any detectable ras mutations, the precise contribution of aberrant Ras function, if any, to endometerial carcinoma development remains to be determineed. Since there is considerable evidence that Ras-transformation is associated with a decreased requirement growth factors, we compared the growth response of endometrial carcinoma cells harboring wild type (Ishikawa cells)or mutated (HHUA cells)K-ras to epidermal growth factor (EGF). First, we determined that both tumor cells expressed comparable levels of the EGF receptor. Next, we observed that EGF could stimulate the growth of Ishikawa, but not HHUA,cells. Furthermore, EGF caused an elevation of Ras-GTP levels in Ishikawa, but not HHUA,cells. However, the introduction of mutated, but not normal, K-ras into Ishikawa cells rendered them nonresponsive to EGF growth stimulation. Thus, the presence of mutated K-ras alone, can modulate the growth response of endometrial carcinoma cells to EGF.Finally, we observed that an inhibitor of the EGF receptor tyrosine kinase activity could prevent soft agar colony formation of Ishikawa cells, but not HHUA or mutant K-ras(12V)-transfected Ishikawa cells. Taken together, these results suggest that mutated K-ras causes a loss of responsiveness to EGF stimulation and that EGTF receptor function is now dispensable for the growth of mutant Ras-positive endometrial carcinoma cells.
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Research Products
(8 results)